Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15533 | 46822;46823;46824 | chr2:178619720;178619719;178619718 | chr2:179484447;179484446;179484445 |
| N2AB | 13892 | 41899;41900;41901 | chr2:178619720;178619719;178619718 | chr2:179484447;179484446;179484445 |
| N2A | 12965 | 39118;39119;39120 | chr2:178619720;178619719;178619718 | chr2:179484447;179484446;179484445 |
| N2B | 6468 | 19627;19628;19629 | chr2:178619720;178619719;178619718 | chr2:179484447;179484446;179484445 |
| Novex-1 | 6593 | 20002;20003;20004 | chr2:178619720;178619719;178619718 | chr2:179484447;179484446;179484445 |
| Novex-2 | 6660 | 20203;20204;20205 | chr2:178619720;178619719;178619718 | chr2:179484447;179484446;179484445 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | rs1406271344  |
-1.07 | 0.001 | N | 0.16 | 0.09 | 0.475741759771 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/L | rs1406271344 |
-1.07 | 0.001 | N | 0.16 | 0.09 | 0.475741759771 | gnomAD-4.0.0 | 1.5939E-06 | None | None | None | None | N | None | 0 | 2.28885E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs777059640 |
-1.741 | 0.007 | N | 0.269 | 0.272 | 0.594932130068 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| I/T | rs777059640 |
-1.741 | 0.007 | N | 0.269 | 0.272 | 0.594932130068 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs777059640 |
-1.741 | 0.007 | N | 0.269 | 0.272 | 0.594932130068 | gnomAD-4.0.0 | 1.86067E-06 | None | None | None | None | N | None | 2.6743E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.4822E-07 | 0 | 0 |
| I/V | None | None | None | N | 0.159 | 0.123 | 0.404733080969 | gnomAD-4.0.0 | 1.5939E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43386E-05 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.4089 | ambiguous | 0.6767 | pathogenic | -1.906 | Destabilizing | 0.129 | N | 0.489 | neutral | None | None | None | None | N |
| I/C | 0.5916 | likely_pathogenic | 0.8107 | pathogenic | -1.061 | Destabilizing | 0.94 | D | 0.549 | neutral | None | None | None | None | N |
| I/D | 0.7272 | likely_pathogenic | 0.892 | pathogenic | -1.591 | Destabilizing | 0.716 | D | 0.638 | neutral | None | None | None | None | N |
| I/E | 0.4991 | ambiguous | 0.7194 | pathogenic | -1.583 | Destabilizing | 0.418 | N | 0.627 | neutral | None | None | None | None | N |
| I/F | 0.1647 | likely_benign | 0.2879 | benign | -1.384 | Destabilizing | 0.716 | D | 0.559 | neutral | None | None | None | None | N |
| I/G | 0.7041 | likely_pathogenic | 0.8947 | pathogenic | -2.249 | Highly Destabilizing | 0.418 | N | 0.617 | neutral | None | None | None | None | N |
| I/H | 0.4534 | ambiguous | 0.7069 | pathogenic | -1.508 | Destabilizing | 0.983 | D | 0.612 | neutral | None | None | None | None | N |
| I/K | 0.3612 | ambiguous | 0.6064 | pathogenic | -1.294 | Destabilizing | 0.351 | N | 0.621 | neutral | N | 0.413505642 | None | None | N |
| I/L | 0.1201 | likely_benign | 0.1977 | benign | -1.018 | Destabilizing | 0.001 | N | 0.16 | neutral | N | 0.45404702 | None | None | N |
| I/M | 0.1084 | likely_benign | 0.1735 | benign | -0.7 | Destabilizing | 0.017 | N | 0.379 | neutral | N | 0.454756799 | None | None | N |
| I/N | 0.2595 | likely_benign | 0.4336 | ambiguous | -1.066 | Destabilizing | 0.716 | D | 0.633 | neutral | None | None | None | None | N |
| I/P | 0.9721 | likely_pathogenic | 0.9855 | pathogenic | -1.285 | Destabilizing | 0.836 | D | 0.636 | neutral | None | None | None | None | N |
| I/Q | 0.3574 | ambiguous | 0.594 | pathogenic | -1.273 | Destabilizing | 0.836 | D | 0.644 | neutral | None | None | None | None | N |
| I/R | 0.3088 | likely_benign | 0.5443 | ambiguous | -0.672 | Destabilizing | 0.655 | D | 0.638 | neutral | N | 0.428578424 | None | None | N |
| I/S | 0.3197 | likely_benign | 0.5564 | ambiguous | -1.666 | Destabilizing | 0.264 | N | 0.568 | neutral | None | None | None | None | N |
| I/T | 0.2157 | likely_benign | 0.4349 | ambiguous | -1.547 | Destabilizing | 0.007 | N | 0.269 | neutral | N | 0.382647847 | None | None | N |
| I/V | 0.0734 | likely_benign | 0.1197 | benign | -1.285 | Destabilizing | None | N | 0.159 | neutral | N | 0.347938344 | None | None | N |
| I/W | 0.7229 | likely_pathogenic | 0.8713 | pathogenic | -1.48 | Destabilizing | 0.983 | D | 0.627 | neutral | None | None | None | None | N |
| I/Y | 0.4063 | ambiguous | 0.566 | pathogenic | -1.277 | Destabilizing | 0.836 | D | 0.585 | neutral | None | None | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.